VIRACEPT FAILING NOW WHAT

Oct 16, 2000

I HAVE BEEN ON COMBINATION THERAPY SUCCESSFULLY SINCE THE LAST THREE YEARS ON [D4T+3TC+VIRACEPT].FOR THREE YEARS MY VIRAL LOAD HAD BEEN ON UNDETECTABLE LEVELS .WHEN I STARTED MY VL WAS 780000 COPIES WHICH WENT DOWN TO UNDETECTABLE LEVELS AFTER MED.

NOW AFTER THREE YEARS I HAVE STARTED FEELING FATIGUED AGAIN...AND MY VLOAD HAD ALSO RISEN TO 87000 COPIES...PLEASE ADVISE SHOULD I CHANGE COMBINATION ,TRY ANOTHER PI OR PLEASE TELL ME WHICH IS THE MOST EFFECTIVE COMB. NOW...I AM FROM INDIA AND EAGERLY AWAIT YOUR ADVISE..

KR.

Response from Dr. Cohen

Well, greetings to you in India. Glad to see how this site is useful around the world.

The first question we ask here is WHY this didn't work for you. And try to see if we can fix that before the next combo. Since your viral load was controlled for three years it is worth looking back to see if something went wrong that we can fix. The most common is missing doses over time -- since we have noted that it is just hard to take pills even twice a day every day. The Viracept has to be taken with meals to be absorbed -- and low blood levels from either missing doses or lack of food could allow HIV to grow back. There are other possible reasons why this would no longer work -- including the possibility that over time any regimen can lose its potency -- since these triple combos may not be 100% successful in stopping the growth of HIV -- and after a few years what little HIV is growing eventually creates enough resistant virus to regrow. This is a particular worry for you with your pretty high pre-treatment viral load -- the higher it is the more potent the regimen must be in order to maintain success.

So what to do? Well, if you can get it -- one approach is to get a genotype and/or phenotype of your HIV. These tests, called resistance tests, allow us to see how your HIV has changed in response to this combo, and this gives us a clearer sense of what should work well this next time. If these tests are not available, then we rely on our prior studies which have looked at the HIV from combinations like yours, and can make some good guesses as to what should work. One of the possible benefits of Viracept is that as HIV starts to grow on it, HIV mutates in ways that don't lead to broad "cross resistance" meaning many of the other protease inhibitors have a good chance of still working for you -- although there is some chance of cross resistance -- and that is why a test can still help -- to see what happened for you.

With or without a test -- if this was your first combo -- the next step would usually include some combination of the following meds: ddI, abacavir, a nonnucleoside (efavirenz or nevirapine would be the two more commonly chosen here) and one or two protease inhibitors. In the PI class you have options of not only which PI, but which dose strategy to pick, since there is a newer concept of "boosted" PIs using a low dose of ritonavir to boost the blood level of a second PI including either saquinavir, indinavir, amprenavir, and at least here in the US the newest called Kaletra (which already has the booster dose of ritonavir in the capsule). Given your potential for a high viral load, we likely would suggest a four drug combo here -- and using the nonnucleoside at this increases your chances for success. There are studies underway to compare different "boosted" PIs -- for example, one is comparing saquinavir to indinavir, each with 100 mg of ritonavir taken twice a day. Other studies planned might compare boosted amprenavir to kaletra.

But this next move is a key one -- since there are far fewer rescues if this next combo doesn't work out -- so please try to locate a clinician who is skilled in HIV treatment, and then monitor your viral load on it. If your viral load on this next combo gets to undetectable using a 50 copy test (or even lower than that) it should work for years. If you don't get to below 50 copies, you might need to further intensify the combo to make it work for you.

And as a side note -- you don't mention your cd4 count. If it is on the lower side -- then it is important to make this next switch now. On the other hand, if your cd4 count is higher, somewhere above 400 to 500 -- some clinicians are exploring a strategy where you would take a pause before just switching to your next combo. Another complexity in the mix...

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